Differential induction of sister chromatid exchanges by indirect-acting mutagen-carcinogens at early and late stages of embryonic development.
To examine the development of drug-metabolizing enzyme systems in the early chick embryo, the procarcinogens, aflatoxin B1 (AF-B1) and 2-acetylamino-fluorene (2-AAF), and the direct-acting carcinogen, ethyl methanesulfonate (EMS) (positive control), were given to embryos; the sister-chromatid-exchange (SCE) technique was used as an indicator of conversion to active mutagenic metabolites. Chick embryos at two stages of incubation (3-day and 6-day) were exposed to the same graded series of dosages of the compounds for a period of 22 hours. All three mutagens increased the frequency of SCE above the control rate of 1,8 SCEs/cell. While a dose-dependent increase in SCE was obtained for both procarcinogens at each age, the mean SCE frequency was significantly higher in the 6-day embryos for each dosage given. In contrast, the direct-acting mutagen, EMS,. gave a reduced level of SCEs at the older age. These results suggest that the ability of early chick embryos to activate promutagens to forms capable of inducing SCE increases as development advances from three to six days of incubation (DI). In the 6-day embryo, the metabolic conversion is enhanced, resulting in a significant increase in the mutagenicity of the test chemicals.
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002642:Chick Embryo / Q000187:drug effects* / Q000502:physiology; D003434:Crossing Over, Genetic / Q000187:drug effects*; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D008940:Mitotic Index / Q000187:drug effects; D009153:Mutagens / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000348:Aflatoxins; D002273:Carcinogens; D009153:Mutagens; D005020:Ethyl Methanesulfonate; D015073:2-Acetylaminofluorene; D016604:Aflatoxin B1